title: Loss of ABCB7 gene: pathogenesis of mitochondrial iron accumulation in erythroblasts in refractory anemia with ringed sideroblast with isodicentric (X)(q13).
abstract: An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of the ABCB7 (ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level of ABCB7 mRNA in the patient's bone marrow cells. Further FISH analyses showed that the ABCB7 gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss of ABCB7 due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan. satofam@asahikawa-med.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sato
authors.affiliation: Oncology Center, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Torimoto
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hosoki
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Department of Medical Laboratory and Blood Center, Asahikawa Medical University Hospital, Asahikawa, Hokkaido, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Naoka
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ichiki
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Shindo
authors.affiliation: Kamifurano Town Hospital, Kamifurano, Hokkaido, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mizukami
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Otake
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Kastunori
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2 jo 1 chome 1-1, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000368:Aged; D000753:Anemia, Refractory / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics* / Q000378:metabolism; D004900:Erythroblasts / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: C113037:ABCB7 protein, human; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D007501:Iron